1. Field of the Invention
The present invention relates to methods for producing optically active amine compounds using ω-transaminases, and more specifically to methods for resolving racemic amines or amino acids into optically active amines or amino acids using ω-transaminases as biocatalysts.
2. Description of the Related Art
Chiral molecules are like left and right hands, which are not superimposable on their mirror images. The word “chiral” comes from the Greek word “chir-” for hand. Chiral compounds are optically active (that means they have the ability to rotate polarized light). In such a sense, a drug whose two molecules exist as enantiomers because of their three-dimensional structures, which cannot be superimposed onto each other, is considered as a “chiral pharmaceutical drug.” Production of optically pure chiral compounds has attracted growing attention. Particularly, chiral amines or chiral amino acids play vital roles in the pharmaceutical, agrochemical, and chemical industries.
Chiral amines are used as indispensable building blocks for a number of pharmaceutical drugs including (S)-rivastigmine for treatment of Alzheimer's disease, dilevalol as an antihypertensive drug, sitagliptin as an antidiabetic drug and mexiletine as an antiarrhythmic and antimyotonic drug. Owing to the pharmaceutical importance of the chiral amines, biocatalytic approaches to produce the optically active chiral amines such as kinetic resolution, asymmetric synthesis, and deracemization have been extensively studied for developing greener alternatives to chemical processes including preferential crystallization and asymmetric catalytic hydrogenation.
Chiral amino acids are also important compounds in diverse sectors, including pharmaceutical, food, agricultural, and chemical industries. Natural amino acids can be produced by simple processes such as fermentation, while the production of unnatural amino acids by fermentation has not been well established and is thus dependent on the use of biocatalysts or chemical catalysts. Chemical catalysts for the production of unnatural amino acids are very expensive, which is a cause of high costs in the production of unnatural amino acids. Accordingly, biocatalysts are usually employed to produce unnatural amino acids.
ω-transaminase displays high turnover rate, stringent enantioselectivity, high stability and no requirement of external cofactor regeneration. Due to these advantages, ω-transaminase has attracted considerable attention as effective biocatalysts for the production of chiral compounds. Particularly, methods for producing optically active amines or amino acids have emerged that include providing an α-keto acid as an amino acceptor substrate, together with ω-transaminase, and kinetically resolving a racemic compound for deracemization. The reasons for the use of the α-keto acid as an amino acceptor are low enantiomeric excess, severe enzyme inactivation, and chemical toxicity of conventional cheap amino acceptors such as propanal and butanol. The α-keto acid is free from such problems but its high cost inevitably leads to an increase in the production cost of the final optically active compounds. In an attempt to produce an optically active compound at reduced cost, Korean Patent Registration No. 10-1291586 reports the use of a fusion protein of vitreoscilla hemoglobin and D-amino acid oxidase. The application of this method is, however, limited to the resolution of homoalanine.